PMID- 23345620
OWN - NLM
STAT- MEDLINE
DCOM- 20130502
LR  - 20211021
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 41
IP  - 5
DP  - 2013 Mar 1
TI  - Development of bis-locked nucleic acid (bisLNA) oligonucleotides for efficient 
      invasion of supercoiled duplex DNA.
PG  - 3257-73
LID - 10.1093/nar/gkt007 [doi]
AB  - In spite of the many developments in synthetic oligonucleotide (ON) chemistry and 
      design, invasion into double-stranded DNA (DSI) under physiological salt and pH 
      conditions remains a challenge. In this work, we provide a new ON tool based on 
      locked nucleic acids (LNAs), designed for strand invasion into duplex DNA (DSI). 
      We thus report on the development of a clamp type of LNA ON-bisLNA-with capacity 
      to bind and invade into supercoiled double-stranded DNA. The bisLNA links a 
      triplex-forming, Hoogsteen-binding, targeting arm with a strand-invading 
      Watson-Crick binding arm. Optimization was carried out by varying the number and 
      location of LNA nucleotides and the length of the triplex-forming versus 
      strand-invading arms. Single-strand regions in target duplex DNA were mapped 
      using chemical probing. By combining design and increase in LNA content, it was 
      possible to achieve a 100-fold increase in potency with 30% DSI at 450 nM using a 
      bisLNA to plasmid ratio of only 21:1. Although this first conceptual report does 
      not address the utility of bisLNA for the targeting of DNA in a chromosomal 
      context, it shows bisLNA as a promising candidate for interfering also with 
      cellular genes.
FAU - Moreno, Pedro M D
AU  - Moreno PM
AD  - Department of Laboratory Medicine, Clinical Research Center, Karolinska 
      Institutet, 141 86 Huddinge, Stockholm, Sweden.
FAU - Geny, Sylvain
AU  - Geny S
FAU - Pabon, Y Vladimir
AU  - Pabon YV
FAU - Bergquist, Helen
AU  - Bergquist H
FAU - Zaghloul, Eman M
AU  - Zaghloul EM
FAU - Rocha, Cristina S J
AU  - Rocha CS
FAU - Oprea, Iulian I
AU  - Oprea II
FAU - Bestas, Burcu
AU  - Bestas B
FAU - Andaloussi, Samir El
AU  - Andaloussi SE
FAU - Jorgensen, Per T
AU  - Jorgensen PT
FAU - Pedersen, Erik B
AU  - Pedersen EB
FAU - Lundin, Karin E
AU  - Lundin KE
FAU - Zain, Rula
AU  - Zain R
FAU - Wengel, Jesper
AU  - Wengel J
FAU - Smith, C I Edvard
AU  - Smith CI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130123
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Buffers)
RN  - 0 (DNA, Superhelical)
RN  - 0 (Oligonucleotides)
RN  - 0 (locked nucleic acid)
RN  - 0 (triplex DNA)
RN  - 9007-49-2 (DNA)
RN  - EC 3.1.21.- (DNA Restriction Enzymes)
SB  - IM
MH  - Base Pairing
MH  - Base Sequence
MH  - Binding Sites
MH  - Buffers
MH  - DNA/chemistry
MH  - DNA Cleavage
MH  - DNA Restriction Enzymes/chemistry
MH  - DNA, Superhelical/*chemistry
MH  - Hydrogen-Ion Concentration
MH  - Molecular Sequence Data
MH  - Oligonucleotides/chemical synthesis/*chemistry
MH  - Plasmids/chemistry
MH  - Transition Temperature
PMC - PMC3597675
EDAT- 2013/01/25 06:00
MHDA- 2013/05/03 06:00
PMCR- 2013/01/23
CRDT- 2013/01/25 06:00
PHST- 2013/01/25 06:00 [entrez]
PHST- 2013/01/25 06:00 [pubmed]
PHST- 2013/05/03 06:00 [medline]
PHST- 2013/01/23 00:00 [pmc-release]
AID - gkt007 [pii]
AID - 10.1093/nar/gkt007 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2013 Mar 1;41(5):3257-73. doi: 10.1093/nar/gkt007. Epub 2013 
      Jan 23.